title: Low concentrations of estradiol reduce beta-amyloid (25-35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells.
abstract: The present studies were undertaken to determine the role of physiologically relevant concentrations of estrogens on amyloid-induced changes in cell viability, metabolic demands, and lipid peroxidation in response to the toxic fragment of beta-amyloid (betaAP 25-35). To this end, SK-N-SH human neuroblastoma cells were exposed to betaAP 25-35 or betaAP 25-35 plus 17beta-estradiol, and cell viability, media glucose use and lactate production were measured at time points ranging from 3 to 15 h for examination of acute effects, or at 48 and 72 h time points for chronic effects. Addition of betaAP 25-35 to SK-N-SH cells decreased the number of viable cells from 5% at 3 h to 35% at 15 h when compared to vehicle controls. Chronic treatment for 48 and 72 h caused decreases in viable cell number of 70% and 65%, respectively. Paradoxically, both glucose utilization and lactate production were found to be increased for the betaAP-treated cells. Concomitant estrogen treatment was found to be neuroprotective, as the severity of the insult on cell viability was decreased by 40% at 15 h and up to 71% at 72 h. Likewise, the addition of 17beta-estradiol decreased both the glucose use and lactate production of the cells. Chronic treatment with betaAP caused increases in lipid peroxidation over vehicle treated controls of 82% and 78% at 48 and 72 h, respectively, while decreases in peroxidation of 48% were seen with simultaneous estrogen treatment. These results indicate that the neuroprotective effects of estrogens against betaAP-induced toxicity are due in part to their capability to decrease lipid peroxidation and may additionally be attributable to decreasing the metabolic load of the cell.
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Gridley
authors.forename: P S
authors.initials: PS
authors.lastname: Green
authors.forename: J W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D019344:Lactic Acid; D004958:Estradiol; D005947:Glucose